Identification and Characterization of aBrucella abortusATP-Binding Cassette Transporter Homolog toRhizobium melilotiExsA and Its Role in Virulence and Protection in Mice

Abstract

Brucella abortus is a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans. The mechanism of virulence of Brucella spp. is not fully understood yet. Furthermore, genes that allow Brucella to reach the intracellular niche and to interact with host cells need to be identified. Using the genomic survey sequence (GSS) approach, we identified the gene encoding an ATPbinding cassette ( Brucellosis is a major zoonotic disease that causes abortion in domestic animals and undulant fever in humans. Brucella proliferates within macrophages of the host and thereby successfully bypasses the bactericidal effects of phagocytes (26,34). Thus, Brucella virulence is associated with the capacity of the organisms to multiply inside the host cells. Therefore, cell-mediated immunity and subsequent activation of macrophages are essential for host clearance of infection (16). Once inside cells, Brucella prevents fusion of the phagosome with the lysosome by altering the intracellular traffic of the early phagosome vesicle (24). It has recently been demonstrated that brucellae replicate in a vesicle compartment containing reticuloendoplasmic markers reached after fusion between phagosomes and lysosomes is prevented (25). However, the genes that allow Brucella to invade and reach the appropriate intracellular replication niche remain to be identified.

Role of Toll-Like Receptor 4 in Induction of Cell-Mediated Immunity and Resistance toBrucella abortusInfection in Mice

“…In addition to improve our understanding of Brucella pathogenesis our findings have an important implication in vaccine development. At similar concentrations, the Brucella S vaccine strain (S19) induces higher protection than the R vaccine strain (RB51) (46). The lack of protective antibodies to the O side chain of the LPS in animals immunized with B. abortus RB51 may explain in part why the R strain induces lower protection against infection (49).…”

Isolation and Characterization of Mini-Tn 5 Km2 Insertion Mutants of Brucella abortus Deficient in Internalization and Intracellular Growth in HeLa Cells

“…The cydC mutant of S. flexneri forms markedly smaller plaques, has markedly decreased intracellular survival, and shows a 100-fold increase in lethal dose for mice compared to the wild type (46). Recently, the role of the ABC transporter in B. abortus virulence, which is homologous to Rhizobium meliloti ExsA, was described (36). Decreased survival in mice of the B. abortus ABC transporter mutant compared to the survival of the wild-type strain shows that the ABC transporter is critical for full bacterial virulence (36).…”

ATP-Binding Cassette Transporters Are Targets for the Development of Antibacterial Vaccines and Therapies

“…For example, mice immunized with a Brucella abortus mutant having a deletion in a virulence gene encoding the ABC-containing protein ExsA exhibited superior protective immunity against virulent B. abortus challenge compared to mice immunized with commercial vaccine strains (63). Furthermore, since ABC transporters may be immunogenic, they might also be exploited as candidate subunits for vaccination against pathogenic bacteria.…”